Mouse F1 spleen cells develop cytotoxic activity in vitro against parental cells. The antigenic differences detected appear to be controlled by a structural gene (Hh-1) mapping on or near the D region of the H-2 complex. Although a number of positive correlations have been demonstrated between murine hemopoietic graft rejection in vivo and F1 anti-parent cytotoxicity in vitro, certain differences have been recently found between these two F1 anti-parent reactions. These include the observations that marrow graft rejection does not require priming and is not dependent upon thymus-dependent cells, whereas the development of cytotoxic cells requires sensitization and is effected by T-lymphocytes. The same mechanism is also responsible for the rejection of hemopoietic allografts. It has been possible, with the use of radiation chimeras, to demonstrate allogenic T-cell mediated cytotoxicity against Hh determinants. A number of parallels were observed among NK cell activity, F1 anti-parent marrow graft rejection in vivo, and F1 anti-parent cytotoxic potential (as well as that against fetal calf serum components) was enhanced by injecting responding cell donors with cells enriched for NK activity.